The research program proposed herein has two major objectives: the development of a new class of reagents for chiral hydroboration, and the synthesis of the ansa bridge of rifamycins. A conceptually New Approach to Chiral Hydroboration. The utility of existing borane reagents for conversion of olefins to chiral alcohols (e.g., diisopinocampheylborane dimer) is severely limited, since greater than 90 percent enantiomeric excess has been achieved only with cis-disubstituted olefins and a few phenyl-containing trisubstituted alkenes. We wish to develop a general method for chiral hydroboration which is applicable to trans-disubstituted and trisubstituted olefins. Our approach is based upon a new class of monomeric boranes in which the boron atom is intramolecularly coordinated to a Lewis base (i.e., and ether, sulfide, or amino group). The requisite reagents should be readily available by hydroboration of chiral, unsaturated ethers, sulfides, and amines. We will also study the preparation of chiral boranes by in situ resolution of racemic organoboranes with chiral amines. A general method for chiral hydroboration would have wide applicability in the synthesis of biologically active molecules. Synthesis of the Ansa Bridge of Rifamycins. We also propose a convergent, highly efficient synthesis of the ansa bridge of rifamycins. Rifampin, a prominent member of this class of antibiotics, is a widely used, orally active antituberculine agent. Whereas several syntheses of the aromatic nucleus of rifamycins have been achieved, only a single route to the stereochemically complex ansa subunit has been disclosed. Key features of our scheme include as enantioselective monohydroboration of an achiral diene, a new selective oxidation-protection of a primary-secondary diol, and a new approach to the pentadienoic ester moiety. While the endomembrane system, which consists of nuclear envelope, endoplasmic reticulum, Golgi apparatus, secretory vesicles, and plasma membrane, functions in synthesis and exocytosis of secretory products from eukaryotic cells, much remains to be learned about the integrated functions of this system. In the differentiated mammary epithelial cell, exocytotic discharge of the constituents of milk involves net discharge of cell surface membrane. In this proposal continuation studies on the role of endomembranes in synthesis, postsynthetic modification and secretion of the constituents of milk are outlined. Specifically, the proposed study is